WHO/BS/2014.2249 An international collaborative study to calibrate the 4th WHO IS for Plasmin (13/206)

Overview

Stocks of the existing WHO 3rd International Standard (IS) for Plasmin (97/536) are low and a replacement is required. One candidate material, donated by a manufacturer, was formulated and lyophilised into sealed ampoules and coded 13/206. An international collaborative study was organized to assign a potency value to 13/206 relative to the current IS (97/536). A total of 16 laboratories from 12 different countries were recruited to take part in the study, of which 15 laboratories returned results. The candidate material was included in the study as coded duplicate samples labeled A and B and potency estimates were obtained using chromogenic and fibrinolytic methods. A potency estimate was determined for 13/206 based on 52 independent chromogenic assay results from 14 laboratories. Fibrinolytic assays were insufficiently represented in the study to assign a potency to an IS; a potency estimate for 13/206 is therefore proposed based on chromogenic assay methods, which is consistent with the calibration of the existing IS (97/536). A laboratory geometric mean was calculated for each laboratory’s results (based on data from samples A and B) and an overall geometric mean of laboratory means was used to potency assign the candidate IS (13/206), which was determined to be 8.0 IU per ampoule with a between laboratory coefficient of variation (GCV) of 7.8 %. It is proposed that preparation 13/206 is established as the WHO 4th International Standard for Plasmin, with a potency of 8.0 IU per ampoule.